Bridging the Gap: A Critical Analysis of Pre-Clinical Wound Healing Models for Improved Translation to Clinical Efficacy

Abstract

Wound healing is a complex process crucial for maintaining tissue integrity. While human trials offer the ultimate testing ground for wound treatments, ethical and practical limitations necessitate pre-clinical models. This review explores the strengths and limitations of various animal models used in wound healing research. The article highlights the contributions of rodents and pigs in elucidating fundamental wound management principles. However, it emphasizes the lack of a perfect model due to inter-species anatomical and physiological variations. Additionally, factors like age, sex, and wound location can influence results. The review then categorizes wound healing models into in vitro (cultured cells), ex vivo (tissues), and in vivo (whole animals) approaches. Each category encompasses various sub-models suitable for studying specific aspects of wound healing. Strengths of pre-clinical models include efficient data generation, controlled environments, and the ability to test therapies in disease states like diabetes. However, limitations include discrepancies in healing mechanisms between species and the difficulty of replicating complex chronic wounds. The review concludes by discussing how incorporating patientderived cells and advanced technologies like induced pluripotent stem cells (iPSCs) and microengineering hold promise for developing more accurate pre-clinical models. This can ultimately expedite drug development and improve wound management in humans.